The Role of Microglia in Neuroblast Migration in the Olfactory System

项目摘要：小胶质细胞在嗅觉系统神经母细胞迁移中的作用 嗅觉系统的独特之处在于它对环境侮辱的脆弱性和再生能力。 嗅球中的中间神经元细胞死亡通过用新的神经元取代这些细胞而得到改善 能够集成到先前建立的神经回路中。小胶质细胞可能在这一过程中起关键作用，因为 他们是细胞死亡的第一线响应者，负责清理碎片。也有越来越多的 近年来对这些免疫细胞在建立神经回路中所起的作用的认识 发展。此外，有证据表明，小胶质细胞可能会招募针对嗅球的神经母细胞。 中风后的受伤部位。小胶质细胞可能影响神经母细胞迁移的机制是 不是很好理解，但嗅觉系统提供了一个易于处理的模型。因此，这个项目将探索 小胶质细胞影响神经母细胞发育过程中的迁移和对细胞死亡的反应的假设 嗅球。 研究小胶质细胞如何影响嗅觉系统中的神经母细胞迁移的三个独立问题 都在这里写的。目的1研究小胶质细胞在脑内的分布和形态。 发展嗅觉系统。假设小胶质细胞的形态反映了功能状态，并且 初步研究表明，小胶质细胞在出生后早期表现出更广泛的形态。 期间，包括沿迁移的神经母细胞的路径存在小的“阿米巴”细胞。这些 “变形虫”细胞可能在神经母细胞迁移流中发挥作用。目标2将检验这一假设 在发育过程中，小胶质细胞的枯竭会导致神经母细胞迁移受阻。初步数据 表明在嗅觉系统中，小胶质细胞与迁移的神经母细胞密切相关。 在星形细胞和血管支架形成之前，引导这些细胞进入 成人期。如果小胶质细胞耗尽导致神经母细胞在到达最后阶段之前聚集和死亡 目的在嗅球，这将提示小胶质细胞促进神经母细胞迁移的功能作用 在这一发育时期。目标3将测试小胶质细胞分泌的分子 影响神经元迁移。荧光原位杂交和免疫组织化学方法将 用于检测沿神经母细胞迁移路径的小胶质细胞分泌分子的表达，两者 在发育过程中，以及对嗅球神经细胞死亡的反应。了解小胶质细胞是如何 调节神经母细胞在嗅觉系统中的迁移不仅会增加我们对嗅觉的理解，而且 可能会为更好的治疗铺平道路，以减轻神经发育障碍和神经损伤。

Project Summary: The Role of Microglia in Neuroblast Migration in the Olfactory System The olfactory system is unique in both its vulnerability to environmental insults and its regenerative capacity. Interneuron cell death in the olfactory bulb is ameliorated by the replacement of these cells with new neurons capable of integrating into previously established neural circuits. Microglia may be pivotal to this process, as they are first-line responders to cell death and are responsible for clearing debris. There has also been growing appreciation in recent years for the role these immune cells play in establishing neural circuits during development. Moreover, there is evidence that microglia may recruit neuroblasts targeted to the olfactory bulb to sites of injury following stroke. The mechanisms by which microglia may influence neuroblast migration is not well understood, but the olfactory system offers a tractable model. Thus, this project will explore the hypothesis that microglia influence neuroblast migration during development and in response to cell death in the olfactory bulb. Three independent questions examining how microglia may affect neuroblast migration in the olfactory system are addressed here. Aim 1 will characterize the distribution and morphology of microglia in the developing olfactory system. It is hypothesized that microglia morphology reflects functional states, and preliminary studies show that microglia exhibit a greater range of morphologies during the early postnatal period, including the presence of small “ameboid” cells along the path of migrating neuroblasts. These “ameboid” cells may play a functional role in neuroblast migratory streams. Aim 2 will test the hypothesis that microglia depletion results in arrested neuroblast migration during development. Preliminary data indicates that microglia closely associate with migrating neuroblasts in the olfactory system during development and prior to the formation of the astrocytic and vascular scaffold that guides these cells in adulthood. If microglia depletion results in neuroblasts clumping and dying before they reach their final destination in the olfactory bulb, it would suggest a functional role for microglia facilitating neuroblast migration during this developmental period. Aim 3 will test the hypothesis that microglia secrete molecules that influence neuron migration. Fluorescence in situ hybridization and immunohistochemical approaches will be used to examine the expression of microglia-secreted molecules along the path of neuroblast migration, both during development and in response to neuron cell death in the olfactory bulb. Understanding how microglia mediate neuroblast migration in the olfactory system will not only increase our understanding of olfaction but may pave the way for better therapies to mitigate neurodevelopmental disorders and neurologic injury.